Salvage therapies for radiation-relapsed isocitrate dehydrogenase-mutant astrocytoma and 1p/19q codeleted oligodendroglioma.
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ABSTRACT: Background
Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches.Methods
Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or nonalkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis.Results
Recurrent Oligo (n = 35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, P = .002) and OS (median: 6.3 vs 1.5 years, respectively, P < .001) than Astro (n = 59). Overall, 90% of recurrences were local. Eight-three percent received AC as the first-line SST; 50% received salvage surgery before SST; approximately 50% with local failure >2 years after prior RT received reirradiation. On MVA, non-AC was associated with worse OS for both Oligo and Astro; salvage surgery was associated with improved PFS and OS for Astro; early reirradiation was associated with improved PFS for Astro.Conclusions
Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment.
SUBMITTER: Ma S
PROVIDER: S-EPMC8324173 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Codeletion of chromosome arms 1p and 19q (1p/19q codeletion) highly benefits diagnosis and prognosis in gliomas. In this study, we investigated the effect of 1p/19q codeletion on cancer cell metabolism and evaluated possible metabolic targets for tailored therapies. METHODS:We combined in vivo 1H (proton) magnetic resonance spectroscopy (MRS) measurements in human gliomas with the analysis of a series of standard amino acids by liquid chromatography-mass spectroscopy (LC-MS) in human glioma biopsies. Sixty-five subjects with low-grade glioma were included in the study: 31 underwent the MRI/MRS examination, 47 brain tumor tissue samples were analyzed with LC-MS, and 33 samples were analyzed for gene expression with quantitative PCR. Additionally, we performed metabolic tracer experiments in cell models with 1p deletion. RESULTS:We report the first in vivo detection of cystathionine by MRS in 1p/19q codeleted gliomas. Selective accumulation of cystathionine was observed in codeleted gliomas in vivo, in brain tissue samples, as well as in cells harboring heterozygous deletions for serine- and cystathionine-pathway genes located on 1p: phosphoglycerate dehydrogenase (PHGDH) and cystathionine gamma-lyase (CTH). Quantitative PCR analyses showed 40-50% lower expression of both PHGDH and CTH in 1p/19q codeleted gliomas compared with their non-codeleted counterparts. CONCLUSIONS:Our results provide strong evidence of a selective vulnerability of codeleted gliomas to serine and glutathione depletion and point to cystathionine as a possible noninvasive marker of treatment response.
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Project description:BackgroundThere have been no evidence-based guidelines on the optimal schedule for the radiological assessment of 1p/19q-codeleted glioma. This study aimed to recommend an appropriate radiological evaluation schedule for 1p/19q-codeleted glioma during the surveillance period through parametric modeling of the progression-free survival (PFS) curve.MethodsA total of 234 patients with 1p/19q-codeleted glioma (137 grade II and 97 grade III) who completed regular treatment were retrospectively reviewed. The patients were stratified into each layered progression risk group by recursive partitioning analysis. A piecewise exponential model was used to standardize the PFS curves. The cutoff value of the progression rate among the remaining progression-free patients was set to 10% at each scan.ResultsProgression risk stratification resulted in 3 groups. The optimal magnetic resonance imaging (MRI) interval for patients without a residual tumor was every 91.2 weeks until 720 weeks after the end of regular treatment following the latent period for 15 weeks. For patients with a residual tumor after the completion of adjuvant radiotherapy followed by chemotherapy, the optimal MRI interval was every 37.5 weeks until week 90 and every 132.8 weeks until week 361, while it was every 33.6 weeks until week 210 and every 14.4 weeks until week 495 for patients with a residual tumor after surgery only or surgery followed by radiotherapy only.ConclusionsThe optimal radiological follow-up schedule for each progression risk stratification of 1p/19q-codeleted glioma can be established from the parametric modeling of PFS.
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